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Titolo:
NSAID-induced gastric damage in rats: Requirement for inhibition of both cyclooxygenase 1 and 2
Autore:
Wallace, JL; McKnight, W; Reuter, BK; Vergnolle, N;
Indirizzi:
Univ Calgary, Dept Pharmacol & Therapeut, Fac Med, Mucosal Inflammat Res Grp, Calgary, AB T2N 4N1, Canada Univ Calgary Calgary AB Canada T2N 4N1 s Grp, Calgary, AB T2N 4N1, Canada
Titolo Testata:
GASTROENTEROLOGY
fascicolo: 3, volume: 119, anno: 2000,
pagine: 706 - 714
SICI:
0016-5085(200009)119:3<706:NGDIRR>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ASPIRIN-INDUCED ULCERATION; MUCOSAL BLOOD-FLOW; GASTROINTESTINAL TOXICITY; LEUKOCYTE ADHESION; CYCLO-OXYGENASE-2; INFLAMMATION; INDOMETHACIN; MICE; MICROCIRCULATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Wallace, JL Univ Calgary, Dept Pharmacol & Therapeut, Fac Med, Mucosal Inflammat Res Grp, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada Univ Calgary 3330 Hosp Dr NW Calgary AB Canada T2N 4N1 Canada
Citazione:
J.L. Wallace et al., "NSAID-induced gastric damage in rats: Requirement for inhibition of both cyclooxygenase 1 and 2", GASTROENTY, 119(3), 2000, pp. 706-714

Abstract

Background & Aims: Selective cyclooxygenase (COX)-2 inhibitors produce less gastric damage than conventional nonsteroidal anti-inflammatory drugs (NSAIDs), suggesting that NSAIDs cause damage by inhibiting COX-1. We tested this hypothesis in rats by using a selective COX-1 inhibitor (SC-560). Methods: The effects of SC-560, celecoxib (selective COX-2 inhibitor), or a combination of both inhibitors on gastric damage and prostaglandin synthesis were determined. Selectivity of the drugs for COX-1 vs. COX-2 was assessed inthe carrageenan-airpouch model. A COX-1-preferential inhibitor, ketorolac,was also evaluated. The effects of these inhibitors on leukocyte adherenceto vascular endothelium and on gastric blood flow were assessed, Results: SC-560 markedly reduced gastric prostaglandin synthesis and platelet COX-1 activity, but spared COX-2 and did not cause gastric damage. Celecoxib did not affect gastric prostaglandin E-2 synthesis and did not cause gastric damage. However, the combination of SC-560 and celecoxib invariably caused hemorrhagic erosion formation, comparable to that seen with indomethacin, Ketorolac caused damage only at doses that inhibited both COX isoforms, or when given with a COX-2 inhibitor. Celecoxib, but not SC-560, significantly increased leukocyte adherence, whereas SC-560, but not celecoxib, reduced gastric blood flow. Conclusions: Inhibition of both COX-1 and COX-2 is required for NSAID-induced gastric injury in the rat.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/04/20 alle ore 02:20:21